Phagocytosis and LPS‐stimulated production of cytokines and prostaglandin E2 is different in Kupffer cells isolated from the periportal or perivenous liver region

Abstract

Background: Kupffer cells can release pro‐inflammatory mediators and contribute to damage, which often appears in a zonated fashion. Methods: To assess position‐associated functional differences, functions of intact Kupffer cells isolated from either the periportal or perivenous acinar region of rat liver were compared. Results: Kupffer cells from the periportal region phagocytosed 2–3 times more FITC‐labelled zymosan particles than corresponding perivenous cells, as determined by confocal microscopy and fluorescence assay. Periportal cells also produced more TNF‐α and IL‐1β, but less NO and PGE2, compared to perivenous cells and the stimulation by addition of lipopolysaccharides (LPS) was moderate. In contrast, after overnight culture LPS dramatically increased TNF‐α release and significantly more so in perivenous Kupffer cells (26‐fold) than in periportal cells (11‐fold). Conclusion: Our study suggests that periportal Kupffer cells are responsible for a major part of phagocytosis by the liver. The stronger LPS response of recovered perivenous Kupffer cells suggests a dominant role of these cells in pro‐inflammatory events that ultimately may contribute to development of damage in this region.